Local anesthetic mechanism

B. G. Coviao and H. G. VasaHo, Local Anesthetics Mechanism of Action and Clinical Use, Grune and Stratton, New York, 1976. 

Albuquerque ML, Kurth CD. (1993). Cocaine constricts immature cerebral arterioles by a local anesthetic mechanism. Eur J Pharmacol. 249(2) 215-20. 

Adjunct therapy epidural clonidine as an analgesic adjunct enhances both sensory and motor block caused by local anesthetics (mechanism unclear). It also enhances the effect of other spinal analgesics, including intrathecal opioids. Both quality and duration are enhanced when clonidine is combined with these other neuraxial analgesics... 

Oxolamine [959-14-8] (57) is sold in Europe. It is an oxadiazole, and its general pharmacological profile is described (81). The compound possesses analgesic, antiinflammatory, local anesthetic, and antispasmodic properties, in addition to its antitussive activity. Although a central mechanism may account for some of the activity, peripheral inhibition of the cough reflex may be the dominant effect. The compound has been shown to be clinically effective, although it is less active than codeine (82,83). The synthesis of oxolamine is described (84). 

Starmer C.F. Grant A.O. and Strauss, H.C. Mechanisms of use-dependent block of sodium channels in excitable membranes by local anesthetics. Biophys J 46 5-21, 1984. 

It has been proposed that local anesthetics pass nerve membrane by neutral species despite the clinical adminsitration of the cationic form. Experimental molecular information is required for a better understanding of the mechanism. Thus the NMR information can be useful to the anesthetic discharging in membranes. 

The ion-channel blocking mechanism has been widely tested and found to be important in both pharmacology and physiology. Examples are the block of nerve and cardiac sodium channels by local anesthetics, or block of NMDA receptor channels by Mg2+ and the anesthetic ketamine. The channel-block mechanism was first used quantitatively to describe block of the squid axon K+ current by tetraethylammonium (TEA) ions. The effects of channel blockers on synaptic potentials and synaptic currents were investigated, particularly at the neuromuscular junction, and the development of the single-channel recording technique allowed channel blockages to be observed directly for the first time. 

The local anesthetic actions of cocaine are independent of its well-known actions on monoamines. Rather, the local anesthetic effects occur as a consequence of its interaction with voltage-gated Na-i-channels (Matthews and Collins 1983). Cocaine s cerebral vasoconstrictor effects occur through local anesthetic rather than sympathomimetic mechanisms (Albuquerque and Kurth 1993). 

Mechanism of action. Na -channel blocking antiarrhythmics resemble most local anesthetics in being cationic Liillmann, Color Atlas of Pharmacology... 

Mechanism-specific adverse effects. Since local anesthetics block Na+ influx not only in sensory nerves but also in other excitable tissues, they are applied locally and measures are taken (p. 206) to impede their distribution into the body. Too rapid entry into the... 

A mechanism of local anesthetic action in which they serve as sodium channel blockers has been proposed. According to this mechanism, the molecular targets of local anesthetic action are the voltage-requiring sodium channels, which are present in all the neurons. The process of local anesthesia by respective drugs can be schematically represented in the following manner. 

Local anesthetics, when applied at effective concentrations locally to nerve tissue, reversibly block nerve impulse conduction and block somatic sensory, somatic motor and autonomic nerve transmission. Their mechanism of action is based on both... 

Ziconotide is a non-opioid, non-NSAID, non-local anesthetic used for the amelioration of chronic pain. In December 2004 the FDA approved ziconotide for intrathecal administration. The drug is derived from a marine snail toxin. Its mechanism of action has not yet been elucidated. Due to serious side effects or lack of efficacy when delivered through more conventional routes ziconotide must be administered in-trathecally. It s use is considered appropriate only for management of severe chronic pain in patients for whom intrathecal therapy is indicated. 

Mechanism of Action A local anesthetic that blocks nerve conduction in the autonomic, sensory, and motor nerve fibers. Competes with calcium ions for membrane... 

Mechanism of Action An anticholinergicthat relaxes detrusor and other smooth muscle by cholinergic blockade, counteracting muscle spasm in the urinary tract, Thera-peuticEffect Produces anticholinergic, local anesthetic, and analgesic effects, relieving urinary symptoms. 

Mechanism of Action An antiarrhythmicthat prevents sodium current across myocardial cell membranes. Has potent local anesthetic activity and membrane stabilizing effects. Slows AV and His-Purkinje conduction and decreases action potential duration and effective refractory period. Therapeutic Effect Suppresses ventricular arrhythmias. 

Mechanism of Action A surface or local anesthetic which is not chemically related to the "caine" types of local anesthetics. Decreases the neuronal membrane permeability to sodium ions, blocking both initiation and conduction of nerve impulses, therefore inhibiting depolarization of the neuron. Therapeutic Effect Temporarily relieves pain and itching associated with anogenital pruritus or irritation. 

Mechanism of Action Tetracaine causes a reversible blockade of nerve conduction by decreasing nerve membrane permeability to sodium. Therapeutic Effect Local anesthetic. 

Mechanism of Action An amide-type local anesthetic that shortens the action potential duration and decreases the effective refractory period and automaticity in the His-Purkinje system of the myocardium by blocking sodium transport across myocardial cell membranes. Therapeutic Effect Suppresses ventricular arrhythmias. Pharmacokinetics Very rapidly and completely absorbed following PO administration, Protein binding 10%, Metabolized in liver. Excreted in urine. Half-life 15 hr. 

The development of newer agents continues because it is relatively easy to synthesize chemicals with local anesthetic properties. Unfortunately, it is difficult to reduce the toxicity of these compounds because the common side effects of local anesthetics represent extensions of their therapeutic effects. New research into the mechanisms of local anesthetic-induced cardiac and spinal toxicity and identification of alternative drug targets for spinal analgesia (eg, opioid receptors, [Pg.560]

The primary mechanism of action of local anesthetics is blockade of voltage-gated sodium channels (Figure 26-2). 

Local anesthetics have poorly understood effects on inflammation at sites of injury, and these anti-inflammatory effects may contribute to improved pain control in some chronic pain syndromes. At the concentrations used in spinal anesthesia, local anesthetics can inhibit transmission via substance P (neurokinin-1), NMDA, and AMPA receptors in the secondary afferent neurons (Figure 26-1). These effects may contribute to the analgesia achieved by subarachnoid administration. Local anesthetics can also be shown to block a variety of other ion channels, including nicotinic acetylcholine channels in the spinal cord. However, there is no convincing evidence that this mechanism is important in the acute clinical effects of these drugs. High concentrations of local anesthetics in the subarachnoid space can interfere with intra-axonal transport and calcium homeostasis, contributing to potential spinal toxicity. 

Another important reason for preferential blockade of sensory fibers follows directly from the state- and use-dependent mechanism of action of local anesthetics. Blockade by these drugs is more marked at higher frequencies of depolarization. Sensory (pain) fibers have a high firing rate and a relatively long action potential duration. Motor fibers fire at a slower rate and have a shorter action potential duration. Type A delta and C fibers are smaller-diameter fibers that participate in high-frequency pain transmission. Therefore, these fibers are blocked earlier and with lower concentrations of local anesthetics than are the large A alpha fibers. 

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